Amines are important intermediates with extremely diverse possible uses in organic synthesis. The importance in modern organic synthesis is restricted only by limitations in the availability of these classes of compounds. The corresponding carboxylic acids or derivatives thereof are available much more often than the amines, for example as natural products, and therefore all methods for degrading carboxylic acid derivatives to the corresponding amines are per se of great interest. Standard methods for preparing primary amines from carboxylic acids or carboxylic acid derivatives are the Hofmann, Curtius, Schmidt and Lossen degradation reactions.
There is a phenomenal increase in the importance of chemo-, regio- and stereoselective reagents in modern organic synthesis. If, for example, it is wished to convert a particular carboxylic acid group from a complex molecule with numerous functional groups into a primary amine, many of the methods mentioned are unsuitable for selectivity reasons. In addition, azides, hydrazoic acid, bromine or chlorine represent a considerable safety risk.
A highly selective solution to the problem of converting carboxylic acids into primary amines which is applicable also to complex multifunctional molecules often having more than one stereocenter has been lacking to date. Although the known reagents are able to bring about the desired transformations, other groups are often also affected. In many cases, even remote stereocenters are epimerized due to the drastic conditions necessary. In addition, the transformation should be applicable with very mild condition-s, the isolation of the product should be very easy and the removal of the secondary products of the reagent employed should be possible without additional process steps.
It would therefore be very desirable to have a method which is able to convert carboxylic acids by rearrangement into the corresponding primary amines but, at the same time, has very mild reaction conditions and working up which is as simple as possible, and can additionally be employed in commercially useful methods. The known reagents do not solve this problem, as will be demonstrated by some examples: in the Hofmann degradation, carboxamides are degraded by treatment with corrosive and toxic bromine or chlorine and alkali to give the primary amine, with numerous functional groups not being tolerated because of the great reactivity of the halogens employed. In the Curtius degradation, toxic hydrazine or explosive azides are employed, and in the Schmidt degradation toxic hydrazoic acid is employed, the latter likewise being able to cause explosions if not properly handled.